Ascending Dose Study of the Safety and Tolerability of Alirocumab (SAR236553/REGN727) in Japanese Healthy Volunteers

A Randomized, Double-Blind, Placebo-Controlled, Ascending Single-Dose Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered SAR236553 in Japanese Healthy Male Subjects

Primary Objective:

To assess the safety and tolerability of ascending single doses of subcutaneously (SC) administered alirocumab (SAR236553/REGN727) in Japanese healthy male subjects.

Secondary Objectives:

• To assess the pharmacodynamics effect of a single SC dose of alirocumab on serum low-density lipoprotein cholesterol (LDL-C) and other lipids and apolipoproteins such as total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, Triglycerides, Apolipoprotein B, Apolipoprotein A1 and Lipoprotein(a).
• To assess the Pharmacokinetic profile of a single SC dose of alirocumab.
• To assess the immunogenicity of a single SC dose of alirocumab.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Alirocumab (Lyophilized formulation); Drug: Placebo (Lyophilized formulation); Drug: Alirocumab (Solution); Drug: Placebo (Solution)

Detailed Description

4 sequential dose cohorts. Single dose followed by a total observation period of 15 weeks (106 days) for each participant.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subject, between 20 and 65 years inclusive.
• Body weight between 50.0 and 95.0 kg inclusive, body mass index between 18.0 and 30.0 kg/m² inclusive.
• Serum LDL-C levels >100 mg/dL

Exclusion Criteria:

• Subject indicated for the use of statins according to criteria in Adult Treatment Panel (ATP) III Guidelines as updated in 2004
• Significant concomitant illness or history of significant illness such as cardiac, renal, neurological, endocrinological, dermatological, metabolic or lymphatic disease, or any other illness or condition that would adversely affect the subject's participation in this study.
• History or presence of drug or alcohol abuse
• Smoking more than 5 cigarettes or equivalent in any 24 hour period.
• Any medication (including St John's Wort) within 14 days before the inclusion or within 5 times the elimination half-life or pharmacodynamic (PD) half-life of that drug, whichever the longest; any vaccination within the last 28 days.
• Positive reaction to any of the following tests: hepatitis B surface (HBs Ag) antigen, anti-hepatitis B core antibodies (anti-HBc Ab), anti-hepatitis C virus (anti-HCV) antibodies, human immunodeficiency virus (HIV) antigen and antibodies, syphilis.
• Elevated cholesterol due to a secondary cause such as hypothyroidism or alcohol.
• Presence or history of drug hypersensitivity
• Initiation of a new exercise routine or major change to a previous exercise routine within 4 weeks prior to Screening.
• Initiation of a new diet or major change to a previous diet within 4 weeks prior to Screening.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Alirocumab dose 1 versus placebo	Drug: Alirocumab (Lyophilized formulation); Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous; Other Names: SAR236553; REGN727; Drug: Placebo (Lyophilized formulation); Pharmaceutical form: lyophilized formulation Route of administration: Subcutaneous
Experimental: Cohort 2; Alirocumab dose 2 versus placebo	Drug: Alirocumab (Lyophilized formulation); Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous; Other Names: SAR236553; REGN727; Drug: Placebo (Lyophilized formulation); Pharmaceutical form: lyophilized formulation Route of administration: Subcutaneous
Experimental: Cohort 3; Alirocumab dose 3 versus placebo	Drug: Alirocumab (Lyophilized formulation); Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous; Other Names: SAR236553; REGN727; Drug: Placebo (Lyophilized formulation); Pharmaceutical form: lyophilized formulation Route of administration: Subcutaneous
Experimental: Cohort 4; Alirocumab dose 4 versus placebo	Drug: Alirocumab (Solution); Pharmaceutical form: solution Route of administration: subcutaneous; Other Names: SAR236553; REGN727; Drug: Placebo (Solution); Pharmaceutical form: solution Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with Adverse Events	106 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in serum Low-Density Lipoprotein Cholesterol (LDL-C) from baseline to each visit.	106 days
Change in ApolipoproteinB, ApolipoproteinA1 and Lipoprotein(a) from baseline to each visit.	106 days
Change in Total Cholesterol (T-C), High-Density Lipoprotein Cholesterol (HDL-C), Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Triglycerides (TG) from baseline to each visit.	106 days

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Teramoto T, Kobayashi M, Uno K, Takagi Y, Matsuoka O, Sugimoto M, Inoue S, Minami F, Baccara-Dinet MT. Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies). Am J Cardiol. 2016 Jul 1;118(1):56-63. doi: 10.1016/j.amjcard.2016.04.011. Epub 2016 Apr 21.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: September 21, 2011
• First Submitted That Met QC Criteria: October 5, 2011
• First Posted (Estimate): October 7, 2011

Study Record Updates

• Last Update Posted (Estimate): September 28, 2016
• Last Update Submitted That Met QC Criteria: September 27, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal; Pharmaceutical Solutions
• Other Study ID Numbers: TDU12190; U1111-1118-1213 (Other Identifier: UTN)